Introduction: The structural correspondence of
neurodevelopmental impairments related to intrauterine growth
restriction (IUGR) that persists later in life remains elusive.
Moreover, early postnatal stimulation strategies have been proposed to
mitigate these effects. Long-term brain connectivity abnormalities in an
IUGR rabbit model and the effects of early postnatal environmental
enrichment (EE) were explored. Materials and Methods: IUGR
was surgically induced in one horn, whereas the contralateral one
produced the controls. Postnatally, a subgroup of IUGR animals was
housed in an enriched environment. Functional assessment was performed
at the neonatal and long-term periods. At the long-term period,
structural brain connectivity was evaluated by means of
diffusion-weighted brain magnetic resonance imaging and by histological
assessment focused on the hippocampus. Results: IUGR
animals displayed poorer functional results and presented altered
whole-brain networks and decreased median fractional anisotropy in the
hippocampus. Reduced density of dendritic spines and perineuronal nets
from hippocampal neurons were also observed. Of note, IUGR animals
exposed to enriched environment presented an improvement in terms of
both function and structure. Conclusions: IUGR is
associated with altered brain connectivity at the global and cellular
level. A strategy based on early EE has the potential to restore the
neurodevelopmental consequences of IUGR.